The proposed studies are designed to clarify the anatomic organization and transmitter specificity of central neural pathways subserving complementary endocrine and autonomic controls of pituitary-adrenal and cardiovascular responses to stress. Three neuropeptides synthesized by hypothalamic effector neurons, oxytocin (OT), vasopressin (AVP) and corticotropin-releasing factor (CRF), play critical roles in achieving integrated stress and cardiovascular responses. The efferent organization and visceral afferent distribution that provides for coordinated responses remain unclear. Various combinations of axonal transport and immunohistochemical methods will be used at the light and electron microscopic (EM) levels to address that following issues: 1. Peptide Interactions in Effector Neuron Pools. Anterograde tracing (PHA-L) and immunocytochemical methods will be used at the light and EM levels in normal and challenged rats to clarify the route(s) and mechanisms by which OT and AVP are delivered to the hypophyseal portal vasculature. A combined anterograde transport and immunohistochemical method will be used to chart the distribution of CRF-, AVP- and OT-immunoreactive (IR) components of hypothalamic projections to medullary autonomic effector neuron pools. 2. Differentiated Pathways Mediating Visceral Afferent Control. The visceral afferent control of neurosecretory cell groups expressing CRF, OT or AVP is gated initially through the nucleus of the solitary tract (NTS), and may involve catecholaminergic relays in the ventrolateral medulla. To determine the extent to which pathways influencing each peptidergic cell type are anatomically and biochemically differentiated, we will: (a). Chart the distribution of adrenergic projections to the PVH from each of three contributing medullary cell groups, (b). Determine the extent to which noradrenergic projections from the Al catecholamine cell group interact preferentially with magnocellular AVP neurons, (c). Determine the extent to which substance P, a potent modifier of AVP secretion, is contained within the Al projection, (d). Clarify the distributional specificity of recently discovered projections from the NTS that contain somatostatin and FSH-releasing protein, and appear to target OT neurons preferentially, and (e). Determine the organization of projections from the NTS to ventrolateral medullary catecholamine cell groups that project in turn to neurosecretory AVP- or CRF-IR cell groups. This work will provide basic information on a system that is intimately involved in the protection of the organism from stress and the maintenance of cardiovascular homeostasis.